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In sexually active partners, early treatment with antiretroviral therapy compared to delayed treatment decreased the risk of genetically linked HIV-1 transmission to the uninfected partner.
In sexually active partners, early treatment with antiretroviral therapy compared to delayed treatment decreased the risk of genetically linked HIV-1 transmission to the uninfected partner. Additionally, the risk of adverse clinical outcomes was decreased in HIV-1 infected patients with early treatment.
These were the findings of a multicontinent, randomized controlled trial published online ahead of print in The New England Journal of Medicine.
In this trial, researchers randomly assigned (stratified by site) HIV-1 serodiscordant couples to receive either early (n=886) or delayed (n=877) treatment with antiretroviral therapy in the HIV-1 positive partner. Thirteen various antiretroviral agents were used in regimens as appropriate. To be included in the trial, couples had to be in a stable relationship for ≥3 months, report ≥3 episodes of vaginal or anal intercourse during this time, and be willing to disclose HIV-1 status to their partner. The HIV-1 positive partner also had to have a CD4 count between 350 and 550 cells/cm3 and have never received antiretroviral therapy except to prevent maternal transmission to a child. Early treatment was initiated in the HIV-1 infected partner at the time of enrollment whereas delayed treatment was initiated when the CD4 count fell below 250 cells/cm3 or AIDS-associated illness developed.
The primary outcomes included (1) genetically linked HIV-1 transmission amongst partners and (2) earliest occurrence of pulmonary tuberculosis, severe bacterial infection, a World Health Organization stage 4 event, or death in HIV-1 infected patients.
The trial was stopped early by the data and safety monitoring board due to observed benefit of early versus delayed treatment. A total of 39 HIV-1 transmissions were observed over a median follow-up of 1.7 years. Of those 39 cases, 28 were virologically linked transmissions and the risk of transmission was significantly decreased with early versus delayed treatment (adjusted HR 0.04; 95% CI, 0.01–0.27). Multivariate analysis suggested that early treatment and baseline condom use decreased linked HIV-1 transmission while higher viral load increased linked HIV-1 transmission. Regarding the composite clinical end point, the risk was significantly reduced with early versus delayed treatment (adjusted HR=0.59; 95% CI, 0.40–0.88).
The frequency of adverse events, after exclusion of the primary composite events, were found to be similar among HIV-1 infected patients in both early and delayed treatment groups (14% in each). However, grade 3 or 4 laboratory abnormalities were found to be more common in the early treatment group (27% vs 18%, P<.001). The researchers stressed, "The clinical importance of the laboratory abnormalities that were responsible for this difference is unclear."
The researches concluded, "In this trial, we found that early antiretroviral therapy had a clinical benefit for both HIV-1 infected persons and their uninfected sexual partners." They continued, "These results support the use of antiretroviral treatment as a part of a public health strategy to reduce the spread of HIV-1 infection."
This trial was sponsored by the HIV Prevention Trials Network and The National Institute of Allergy and Infectious Disease.
Cohen MS, Chen YQ, McCauley M et al. Prevention of HIV-1 infection with early antiretroviral therapy. NEJM. 2011; Jul 18. [Epub ahead of print]